Phosphatidylinositol turnover in mitogen-activated lymphocytes. Suppression by low-density lipoproteins.
Low-density (LD) lipoproteins inhibit phytohaemagglutinin-enhanced turnover of phosphatidylinositol in human peripheral lymphocytes. Turnover was assessed by (32)P incorporation into phospholipids and by loss of (32)P from [(32)P]phosphatidylinositol. Inhibition of lipid turnover by LD lipoproteins is not the result of a change in the amount of phytohaemagglutinin required for maximum cellular response. Neither phytohaemagglutinin nor LD lipoproteins influence (32)P incorporation into phosphatidylethanolamine and phosphatidylcholine during the first 60min after mitogenic challenge. The extent of inhibition of phosphatidylinositol turnover by LD lipoproteins depends on the concentration of LD lipoproteins present in the incubation medium: 50% of maximum inhibition occurs at a low-density-lipoprotein protein concentration of 33mug/ml and maximum inhibition occurs at low-density-lipoprotein protein concentrations above 100mug/ml. Phytohaemagglutinin stimulates (32)P incorporation into phosphatidylinositol, phosphatidylinositol phosphate and phosphatidylinositol bisphosphate. However, LD lipoproteins abolish (32)P incorporation into phosphatidylinositol without affecting incorporation into phosphatidylinositol phosphate and phosphatidylinositol bisphosphate. The ability of LD lipoproteins to inhibit phytohaemagglutinin-induced phosphatidylinositol turnover is mimicked by EGTA. Furthermore, inhibition of LD lipoproteins by phytohaemagglutinin-induced (32)P incorporation into phosphatidylinositol correlates directly with inhibition by LD lipoproteins of Ca(2+) accumulation. These results suggest that Ca(2+) accumulation and turnover of phosphatidylinositol are coupled responses in lymphocytes challenged by mitogens. The step in phosphatidylinositol metabolism that is sensitive to LD lipoproteins and, by inference, that is coupled to Ca(2+) accumulation is release of [(32)P]phosphoinositol from phosphatidylinositol.
D002118:Calcium / Q000378:metabolism; D003864:Depression, Chemical; D004533:Egtazic Acid / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism*; D010835:Phytohemagglutinins / Q000494:pharmacology
D008077:Lipoproteins, LDL; D010710:Phosphates; D010716:Phosphatidylinositols; D010835:Phytohemagglutinins; D004533:Egtazic Acid; D002118:Calcium